Chagas Disease (American Trypanosomiasis) Workup

  • Author: Louis V Kirchhoff, MD, MPH; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Jun 3, 2011
 

Laboratory Studies

The diagnosis of acute Chagas disease, which includes congenital Chagas disease and reactivation of chronic T cruzi infection in immunosuppressed persons, is based on direct detection of the parasites. In contrast, the diagnosis of chronic infection (indeterminate or chronic symptomatic phases) is generally based on serologic testing, since the low level of circulating parasites precludes microscopic detection.

  • Parasitologic diagnosis
    • One useful method for identification of parasites in the blood is to put 1.5 µL of anticoagulated blood under a 12-mm circular cover slip and examine 200 fields under 400 X magnification.[67] This allows for the examination of 0.44 µL of blood with each round, which should take about 30 minutes of careful looking. The trypomastigotes are translucent; thus, they are usually detected based on the corresponding movement of RBCs. This approach has no set threshold for deciding that the result is negative. Simply stated, the greater the number of fields examined, the greater the probability of detecting a parasite in an acutely infected person.
    • Stained thin and thick blood smears may also be examined microscopically. The author is not aware of any comparative data that shed light on the relative sensitivity of examining stained smears versus wet preparations, although the movement of the parasites in the latter would seem to be advantageous.
    • Another method of evaluation involves using heparinized microhematocrit tubes. This method has been used extensively to test for congenital Chagas disease in infants born to chronically infected mothers.[68] The tubes are typically filled directly from the source and spun. The buffy coat at the interface of the plasma and RBCs is then examined microscopically. The curvature of the tube makes this somewhat difficult, but this problem can be resolved by cutting the tube and examining the buffy coat as if it were fresh blood. This procedure carries a risk of accidental transmission and thus should be performed only by experienced personnel.
    • Indirect parasitologic methods include xenodiagnosis and hemoculture.
      • In xenodiagnosis, 30-40 laboratory-reared insects are allowed to feed directly or indirectly on the blood of a person suspected to have Chagas disease. At least one month later, intestinal contents of the insects are extracted and examined microscopically for the presence of parasites. Xenodiagnosis is tedious, requires a long time to perform, and yields a sensitivity of only 50% in the best of hands.
      • Hemoculture, which involves a specialized liquid culture medium that is not available commercially, takes roughly the same amount of time as xenodiagnosis and has roughly the same level of sensitivity, but it is less tedious.
      • Neither xenodiagnosis nor hemoculture has any reasonable role in the diagnosis of acute Chagas disease, since the results are not available in time for short-term treatment decisions. In addition, their role in diagnosing chronic T cruzi infection is largely limited because of their insensitivity. However, these tests may have a role in resolving borderline serologic results or in evaluating treatment failures. These methods can yield specificity rates of up to 100% in the hands of practitioners who can morphologically differentiate T cruzi from T rangeli, which is co-endemic in some regions. Nonetheless, these methods are being viewed increasingly as historical oddities.
  • Serologic diagnosis
    • Tests for anti– T cruzi immunoglobulin M (IgM) are not standardized, are not available commercially, and play no role in the diagnosis of acute Chagas disease.
    • Serologic testing for specific antibodies to T cruzi is the cornerstone of diagnosing chronic T cruzi infection.
    • More than 30 serologic assays have, at one time, been available in Latin America for testing clinical and donor specimens for chronic T cruzi infection. The most widely used today are indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and indirect hemagglutination. Most use lysates of epimastigotes as target antigens, but several are based on recombinant proteins.
    • Many of the available assays yield suboptimal sensitivity and/or specificity rates. WHO Chagas experts and other authorities have recommended that each specimen undergo testing with two types of assays, and this approach is generally followed for blood donor testing in endemic countries.
    • In the United States, the Ortho T cruzi ELISA Test System is the only assay approved by the FDA for donor screening. Its approval for clinical testing is imminent as of this writing (October 2008). After approval, it will be offered for testing clinical samples by Quest Diagnostics.
    • The Chagas Radioimmune Precipitation Assay (Chagas RIPA) is currently being used by Quest Diagnostics for confirmatory testing of donor specimens that are repeat positive in the Ortho assay.[69] The RIPA is available for research and limited clinical testing in the author’s laboratory at the University of Iowa.
    • Currently, two ELISAs are approved by the FDA for clinical testing (Hemagen Chagas Kit, Hemagen Diagnostics, Inc.; Chagatest ELISA Recombinante v. 3.0, Laboratorios Wiener). For initial testing, the author suggests using the latter through the Division of Parasitic Diseases of the Centers for Disease Control and Prevention (CDC). When the Ortho assay is approved for clinical use, the author recommends that samples be sent to Quest Diagnostics for testing. In all cases, positive and indeterminate results should be confirmed with the Chagas RIPA.
  • Diagnosis via polymerase chain reaction–based assays
    • The use of PCR-based tests for detecting T cruzi has been studied extensively over the past 20 years, and dozens of articles have described this approach.[70]
    • The use of many distinct primer pairs has been described; the accumulated evidence suggests that assays based on TCZ1/TCZ2 (nuclear repetitive sequence)[71] and S35/S35 (kDNA minicircle conserved region)[72] are the most sensitive.
    • Methodologies for PCR-based assays for T cruzi have not been standardized, and no kits are available commercially. In this context, false-positive results have been an intermittent but persistent problem.
    • Although PCR-based assays generally appear to yield better sensitivity rates than xenodiagnosis or hemoculture, it is not high enough to justify their use for primary or confirmatory testing. The variable sensitivity is likely due to the extremely low parasite burden in chronically infected persons, meaning that the small blood samples taken for DNA extraction may not contain even a single parasite.
    • Given the variable sensitivity, the intermittent lack of specificity, and the lack of standardization and commercial availability of PCR-based assays for T cruzi, these tests currently have almost no role in the diagnosis of chronic T cruzi infection other than in the evaluation of treatment failures .
    • PCR-based assays for T cruzi may have a role in detecting acute Chagas disease, particularly congenital T cruzi infection, since their sensitivities have been shown to be greater than microscopic examination in several contexts.[73, 74, 75]
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Imaging Studies

No imaging studies are specific for Chagas disease. However, the manifestations of Chagas disease (eg, cardiac, esophageal, and colonic dysfunction) should be evaluated with the appropriate imaging studies, as they would be when resulting from any disease process.

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Other Tests

  • Electrocardiography and 24-hour continuous monitoring are the cornerstones of assessing possible dysrhythmias in patients with chronic T cruzi infections, as is the case with rhythm disturbances of any cause. Infected persons should undergo electrocardiography every 6-12 months to monitor for the development of ominous arrhythmias that would require suppressive drug treatment or pacemaker placement.
  • Esophageal manometry and endoscopy may be useful in assessing and managing patients with Chagas disease who have symptoms that suggest esophageal dysfunction. Endoscopy can be used to differentiate chagasic megaesophagus from other causes of esophageal dysfunction (eg, cancer).
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Contributor Information and Disclosures
Author

Louis V Kirchhoff, MD, MPH  Professor, Departments of Internal Medicine (Infectious Diseases) and Epidemiology, Carver College of Medicine and College of Public Health, University of Iowa; Staff Physician, Medical Service, Iowa City Veterans Affairs Medical Center

Louis V Kirchhoff, MD, MPH is a member of the following medical societies: American Association of Blood Banks and American Society of Tropical Medicine and Hygiene

Disclosure: Abbott Laboratories, Inc. Consulting fee Consulting; Quest Diagnostics Inc. Consulting fee Consulting; Goldfinch Diagnostics Inc. Salary Equity owner; Quest Diagnostics Inc. Royalty Licensed technology

Specialty Editor Board

Mary D Nettleman, MD, MS, MACP  Professor and Chair, Department of Medicine, Michigan State University College of Human Medicine

Mary D Nettleman, MD, MS, MACP is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

John W King, MD  Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University Health Sciences Center; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, and Sigma Xi

Disclosure: emedicine $50.00 author of chapter; MERCK None Other

Eleftherios Mylonakis, MD  Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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